Glycine, N-acetyl-N-[3-(trifluoromethyl)phenyl]valyl-, ethyl ester

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 13 August 2002 to 18 November 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

17th July 1992

Deviations:

yes

Remarks:

Relative humidity recorded in the animal room was sometimes outside of the target ranges specifiedd in the Study plan. This minor deviation was not considered to have compromised the validity or integrity of the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

31st July 1992

Deviations:

yes

Remarks:

Relative humidity recorded in the animal room was sometimes outside of the target ranges specifiedd in the Study plan. This minor deviation was not considered to have compromised the validity or integrity of the study.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Glycine, N-acetyl-N-[3-(trifluoromethyl)phenyl]valyl-, ethyl ester

EC Number:

609-496-9

Cas Number:

379685-94-6

Molecular formula:

C18H23F3N2O4

IUPAC Name:

Glycine, N-acetyl-N-[3-(trifluoromethyl)phenyl]valyl-, ethyl ester

Test material form:

solid: particulate/powder

Details on test material:

- Other: ochre fine powder

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL- Storage condition of test material: room temperaturepH OF TEST ITEM: approximately 5 at the concentration of 10% in purified water, measured at the testing laboratory.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS - Source: CEGAV, Saint Mars d'Egrenne, France. - Age at study initiation: 2 to 4 months old - Weight at study initiation: 2.8 ± 0.1 kg - Housing: animals were housed individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm). Each cage was equipped with a food container and a water bottle. - Diet: ad libitum to 110 pelleted diet (UAR, Villemoisson, Epinay-sur-Orge, France). Diet was analysed regularly by the supplier for composition and contaminant levels (dietformula was available in the study report). - Water: ad libitum to drinking water filtered by a FG Millipore membrane (0.22 micron). Bacteriological and chemical analyses of water were performed regularly by extemal laboratories (include detection of possible contaminants (pesticides, heavy metals and nitrosamines)). - Acclimation period: at least five days. ENVIRONMENTAL CONDITIONS - Temperature (°C): 18±3°C - Humidity (%): 30 to 70% - Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air. - Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated skin served as control

Amount / concentration applied:

TEST MATERIAL - Amount(s) applied (volume or weight with unit): 0.5 g of the test item in its original form

Duration of treatment / exposure:

4 hours

Observation period:

1 hour, 24, 48 and 72 hours after removal of the dressing. As no persistent irritant reaction was obserevd, the study was ended on day 4.

Number of animals:

3 male rabbits

Details on study design:

TEST SITE - Preparation: 24 hours before treatment, both flanks of each animal were clipped using electric clippers and the skin of each animal was examined. Only animals with healthy intact skin were used. Clipping was repeated thereafter on day 3 for two animals of the study. - Area of exposure: no data - Application: As no irritant effects were anticipated, the test item was applied for 4 hours to three animals. A single dose of 0.5 g of the test item in ils original form was placed on a moistened gauze pad, which was then applied to the right flank of the animals for 4 hours. - Type of wrap if used: The test item and the gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage. REMOVAL OF TEST SUBSTANCE - Washing (if done): after removal of the dressing any residual test item was wiped off by means of a moistened cotton pad. - Time after start of exposure: 4 hoursOBSERVATION TIME POINTS1 hour, 24, 48 and 72 hours after removal oft he dressing. According to the guidelines followed, the study was ended on day 4 in the absence of persistent irritatant reactions.SCORING SYSTEM:Dermal irritation was evaluated for each animal according to the following scoring scale: Erythema and eschar formation: . no erythema........................................................................................................... 0 . very slight erythema (barely perceptible).............................................................. 1 . well-defined erythema........................................................................................... 2 . moderate to sévère erythema................................................................................. 3 . sévère erythema (beet redness) to slight eschar formation (injuries in depth)...... 4 Oedema formation . no oedema............................................................................................................. 0 . very slight oedema (barely perceptible) ................................................................ 1 . slight oedema (edges of area well-defîned by defmite raising)............................. 2 . moderate oedema (raised approximately 1 millimètre)......................................... 3 . sévère oedema (raised more than 1millimètre and extending beyond area of exposure)..................................................................... 4 Any other lesions were noted.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: a score of 1 was obtained at the 1h observation time point

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: a score of 1 was obtained at the 1h observation time point

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: a score of 1 was obtained at the 1h observation time point

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: a score of 0 was obtained at the 1h observation time point

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: a score of 0 was obtained at the 1h observation time point

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: a score of 0 was obtained at the 1h observation time point

Irritant / corrosive response data:

- The readings carried out 1 hour after treatment showed a very slight erythema (grade 1) in all the animals of the study.- The readings carried out 24, 48 and 72 hours after treatment showed that none of the animals presented any lesions.- Individual mean scores for erythema and edema, 24, 48 and 72 hours after treatment were all 0.00 for the three animals.

Other effects:

None.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions of this study, the test material is not classified as irritating to the skin according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) criteria.

Executive summary:

This GLP-compliant study was performed to assess the potential of the test material to induce skin irritation in vivo, according to OECD Guideline 404 (dated July 17th, 1992) and EU method B.4 of the E.E.C. directive n° 92/69 (dated July 31st, 1992).

Material and methods

0.5 g of the solid test material were applied under semi-occlusive dressing during 4 hours, on a clipped skin area of one flank of 3 male rabbits. Skin reactions were recorded 1 hour and then 24, 48 and 72 hours after removal of the dressing.

Results

A very slight erythema was noted in all animals 1h after removal of the dressing. No dermal lesions were observed in any animal at all the other observation time points. The individual mean scores (24, 48 and 72 hours) of all three animals for erythema and edema were both: 0.0, 0.0 and 0.0.

Conclusion

Under the experimental conditions of this study, the test material is not classified as irritating to the skin according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) and the

Globally Harmonized System of Classification and Labelling of Chemicals (GHS) criteria.